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HIV-1 暴露和抗逆转录病毒治疗策略对感染 HIV 的儿童在婴儿期疫苗免疫原性的影响。

Effect of HIV-1 exposure and antiretroviral treatment strategies in HIV-infected children on immunogenicity of vaccines during infancy.

机构信息

aDepartment of Science and Technology/National Research Foundation: Vaccine Preventable Diseases; Johannesburg bMedical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty Health Sciences; University of the Witwatersrand, Faculty of Health Sciences, Johannesburg; cPerinatal HIV Research Unit, University of the Witwatersrand, Faculty of Health Sciences dStellenbosch University, Children's Infectious Diseases Clinical Research Unit, Tygerberg eDivision of National Health Laboratory Service, National Institute for Communicable Diseases, Centre for Vaccines and Immunology, Sandringham, South Africa.

出版信息

AIDS. 2014 Feb 20;28(4):531-41. doi: 10.1097/QAD.0000000000000127.

Abstract

INTRODUCTION

We studied the effect of maternal HIV-exposure and timing of antiretroviral treatment (ART) in HIV-infected infants on antibody responses to combined diphtheria-toxoid-tetanus-toxoid-whole cell pertussis and Haemophilus influenzae type b conjugate vaccine (HibCV) and monovalent hepatitis B vaccine (HBV).

METHODS

HIV-uninfected infants born to HIV-infected (HEU) or HIV-uninfected (HUU) mothers were enrolled in parallel with HIV-infected children with CD4⁺ ≥25%, who were randomized to initiate ART immediately upon confirmation of HIV-infection (ART-Immed) or when clinically and/or immunologically indicated (ART-Def). Infants received three doses of diphtheria-toxoid-tetanus-toxoid -wP-HibC/HBV at 7.3, 11.4 and 15.4 weeks of age. Antibody to diphtheria-toxoid, tetanus-toxoid, pertussis toxin, filamentous hemagglutinin (FHA) and hepatitis B surface antigen (HBsAg) were measured by Luminex multiplex-immunoassay and polyribosyl-ribitol phosphate (PRP) antibodies by standard ELISA and bactericidal assay.

RESULTS

Prevaccination antibody geometric mean concentrations (GMCs) were higher in HUU than HEU infants for tetanus-toxoid, but lower for HBsAg, diphtheria-toxoid and FHA. Postvaccination GMCs and proportion with seroprotective antibody levels or sero-conversion rates were similar between HUU and HEU infants for all vaccines. Postvaccination GMCs were higher in HUU for tetanus-toxoid, diphtheria-toxoid, HBsAg and FHA than ART-Immed infants; and for tetanus-toxoid, HBsAg and pertussis-toxoid than ART-Def infants. Nevertheless, there was no difference in proportion of HUU and HIV-infected infants who developed sero-protective vaccine-specific antibody levels postvaccination. The timing of ART initiation generally did not affect immune responses to vaccines between HIV-infected groups.

CONCLUSION

Vaccination with DTwP-HibCV/HBV of HEU and HIV-infected infants initiated on early-ART confers similar immunity compared with HUU children.

摘要

引言

我们研究了 HIV 感染婴儿的母婴 HIV 暴露和抗逆转录病毒治疗(ART)时机对联合白喉类毒素-破伤风类毒素-全细胞百日咳和流感嗜血杆菌 b 型结合疫苗(HibCV)和单价乙型肝炎疫苗(HBV)抗体反应的影响。

方法

HIV 未感染婴儿与 HIV 感染(HEU)或 HIV 未感染(HUU)母亲同时被纳入研究,这些婴儿与 CD4+≥25%的 HIV 感染儿童一起进行平行研究,后者随机分为在 HIV 感染确诊后立即开始 ART(ART-Immed)或根据临床和/或免疫指征开始 ART(ART-Def)。婴儿在 7、11 和 15 周龄时接受三剂白喉类毒素-破伤风类毒素-全细胞百日咳-HibC/HBV 疫苗。使用 Luminex 多重免疫分析测定白喉类毒素、破伤风类毒素、百日咳毒素、丝状血凝素(FHA)和乙型肝炎表面抗原(HBsAg)的抗体,用标准 ELISA 和多聚核糖基-核糖醇磷酸(PRP)抗体测定测定。

结果

在接种前,HUU 婴儿的破伤风类毒素抗体几何平均浓度(GMC)高于 HEU 婴儿,但 HBsAg、白喉类毒素和 FHA 抗体 GMC 则较低。对于所有疫苗,与 HEU 婴儿相比,HUU 婴儿的接种后 GMC 和具有血清保护性抗体水平或血清转化率的比例相似。与 ART-Immed 婴儿相比,HUU 婴儿的破伤风类毒素、白喉类毒素、HBsAg 和 FHA 的接种后 GMC 更高;与 ART-Def 婴儿相比,HUU 婴儿的破伤风类毒素、HBsAg 和百日咳毒素的 GMC 更高。然而,在接种后获得血清保护性疫苗特异性抗体水平的 HUU 和 HIV 感染婴儿的比例没有差异。ART 开始时间通常不会影响 HIV 感染组之间疫苗的免疫反应。

结论

早期开始 ART 的 HEU 和 HIV 感染婴儿接种 DTwP-HibCV/HBV 疫苗可产生与 HUU 儿童相似的免疫力。

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